We are utilizing thymidine kinase minus mammalian cells to study the details of mitochondrial DNA replication and function. These cells incorporate thymidine and thymidine analogues into mitochondrial DNA. We are also studying the effects of chemotherapeutic drugs known to inhibit DNA synthesis. BIBLIOGRAPHIC REFERENCES: Berk, A.J. and D.A. Clayton, Mechanism of Mitochondrial DNA Replication in Mouse L-Cells: Topology of Circular Daughter Molecules and Dynamics of Catenated Oligomer Formation, J. Mol. Biol. 100:85 (1976). Bogenhagen, D. and D.A. Clayton. The Thymidylate Nucleotide Supply for Mitochondrial DNA Synthesis in Mouse L-Cells: Effect of 5-Fluorodeoxy-uridine and Methotrexate in Thymidine Kinase Plus and Thymidine Kinase Minus Cells. J. Biol. Chem. 251:2938 (1976).